The hypothesis that estrogens unopposed by progesterone promote endometrial cell proliferation, and therefore increase risk of endometrial cancer, is supported by experimental as well as epidemiologic data. Because androgens are the main source of circulating estrogens in postmenopausal women, a positive association of circulating androgens with endometrial cancer risk is also expected. This study will be the first to assess the association of prediagnostic levels of circulating estrogens and androgens with endometrial cancer risk in postmenopausal women. The specific objectives of this project are to: (1) Assess the relation of postmenopausal endogenous estrogens with endometrial cancer risk in a case-control study nested within three prospective cohorts: the New York University Women's Health Study (NYUWHS), the ORDET Study in Milan, Italy, and the Northern Sweden Health and Disease Study in Umea, Sweden; (2) Assess the relation of postmenopausal endogenous androgens with endometrial cancer risk in the same case-control study. For all three cohorts, serum samples collected at enrollment and stored at 80oC are available for biochemical analyses. A case-control study of endometrial cancer and postmenopausal endogenous estrogens nested within the NYUWHS and funded by the NCI (R29 CA66189, PI: A. Zeleniuch- Jacquotte) is already ongoing. The design of this study will be implemented in the two other cohorts. All incident cases diagnosed within the studies will be included. Individually-matched controls will be selected among all subjects from the same cohort with the following characteristics: postmenopausal at entry, alive, free of cancer and with an intact uterus at the time of diagnosis of the case, and matching the case on age at enrollment (+6 months), and date of enrollment (3 months). As is currently done for the NYUWHS participants, data on potential confounders will be collected through telephone interviews for Umea and ORDET participants. Serum samples of all cases and matched controls will be assayed in the same laboratory for estradiol, free-estradiol, estrange, testosterone, androstenedione, DHEA, and SHBG. Combining cases from the three cohorts will result in a total of 140 cases, a much larger number than would be expected in each individual cohort.